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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,10,8]]},"abstract":"<jats:p>\n            <jats:italic>Trypanosoma brucei<\/jats:italic>\n            parasites successfully evade the host immune system by periodically switching the dense coat of variant surface glycoprotein (VSG) at the cell surface. Each parasite expresses\n            <jats:italic>VSGs<\/jats:italic>\n            in a monoallelic fashion that is tightly regulated. The consequences of exposing multiple VSGs during an infection, in terms of antibody response and disease severity, remain unknown. In this study, we overexpressed a high-mobility group box protein, TDP1, which was sufficient to open the chromatin of silent\n            <jats:italic>VSG<\/jats:italic>\n            expression sites, to disrupt\n            <jats:italic>VSG<\/jats:italic>\n            monoallelic expression, and to generate viable and healthy parasites with a mixed VSG coat. Mice infected with these parasites mounted a multi-VSG antibody response, which rapidly reduced parasitemia. Consequently, we observed prolonged survival in which nearly 90% of the mice survived a 30-d period of infection with undetectable parasitemia. Immunodeficient RAG2 knock-out mice were unable to control infection with TDP1-overexpressing parasites, showing that the adaptive immune response is critical to reducing disease severity. This study shows that simultaneous exposure of multiple VSGs is highly detrimental to the parasite, even at the very early stages of infection, suggesting that drugs that disrupt VSG monoallelic expression could be used to treat trypanosomiasis.\n          <\/jats:p>","DOI":"10.1073\/pnas.1905120116","type":"journal-article","created":{"date-parts":[[2019,9,25]],"date-time":"2019-09-25T23:55:11Z","timestamp":1569455711000},"page":"20725-20735","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":23,"title":["African trypanosomes expressing multiple VSGs are rapidly eliminated by the host immune system"],"prefix":"10.1073","volume":"116","author":[{"given":"Francisco","family":"Aresta-Branco","sequence":"first","affiliation":[{"name":"Instituto de Medicina Molecular-Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal;"},{"name":"Division of Immune Diversity, German Cancer Research Center, 69120 Heidelberg, Germany;"},{"name":"Division of Structural Biology of Infection and Immunity, German Cancer Research Center, 69120 Heidelberg, Germany;"}]},{"given":"Margarida","family":"Sanches-Vaz","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular-Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal;"}]},{"given":"Fabio","family":"Bento","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular-Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal;"},{"name":"Institute of Molecular Biology, Johannes Gutenberg Universit\u00e4t, 55128 Mainz, Germany;"},{"name":"Institute of Developmental Biology and Neurobiology, Johannes Gutenberg Universit\u00e4t, 55128 Mainz, Germany"}]},{"given":"Jo\u00e3o A.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular-Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal;"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5752-6586","authenticated-orcid":false,"given":"Luisa M.","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular-Jo\u00e3o Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal;"}]}],"member":"341","published-online":{"date-parts":[[2019,9,25]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1432-1033.1973.tb03026.x","article-title":"A new group of chromatin-associated proteins with a high content of acidic and basic amino acids","volume":"38","author":"Goodwin G. 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